Phase 3
Completed N=596
A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer
Source: ClinicalTrials.gov NCT00950300 ↗Enrolled (actual)
596
Serious AEs
18.5%
Results posted
Jan 2017
Primary outcomePrimary: Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery — 57.8; 78.7 μg/mL
◆ Published Evidence
Highly cited
345citations · ~25 / year
Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial.
Summary
In this open-label multicenter trial, participants with operable or locally advanced breast cancer will be randomized to pre-operative treatment with 8 cycles of chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil, epirubicin, and cyclophosphamide) concurrent with either SC Herceptin or IV Herceptin. After surgery, participants will receive a further 10 cycles of SC or IV Herceptin as per randomization to complete 1 year of treatment. All cycles will be 21 days in length. After the end of study treatment, participants will be followed for safety and efficacy for up to 5 years or until disease recurrence, whichever is earlier.
Linked Publications (2)
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Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial.
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Subcutaneous vs Intravenous Trastuzumab for Patients With ERBB2-Positive Early Breast Cancer: Final Analysis of the HannaH Phase 3 Randomized Clinical Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery |
57.8; 78.7 | — |
| PRIMARY Percentage of Participants With Pathological Complete Response (pCR) |
40.7; 45.4 | — |
| SECONDARY Observed Ctrough of Trastuzumab After Surgery |
62.1; 90.4 | — |
| SECONDARY Predicted Ctrough of Trastuzumab Prior to Surgery |
51.4; 80.3 | — |
| SECONDARY Predicted Ctrough of Trastuzumab After Surgery |
51.7; 80.6 | — |
| SECONDARY Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery |
232; 227 | — |
| SECONDARY Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery |
216; 227 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery |
221; 149 | — |
| SECONDARY Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery |
0.05; 4.12 | — |
| SECONDARY Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery |
2056; 2268 | — |
| SECONDARY Cmax of Trastuzumab After Surgery |
230; 166 | — |
| SECONDARY Tmax of Trastuzumab After Surgery |
0.06; 4.08 | — |
| SECONDARY AUC21d of Trastuzumab After Surgery |
2179; 2610 | — |
| SECONDARY Percentage of Participants With Total Pathological Complete Response (tpCR) |
34.2; 39.2 | — |
| SECONDARY Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at Baseline |
88.8; 87.2 | — |
| SECONDARY Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline |
6.14; 6.14 | — |
| SECONDARY Percentage of Participants Who Experienced a Protocol-Defined Event |
33.3; 32.7 | — |
| SECONDARY Event-Free Survival (EFS) |
NA; NA | 0.8651 |
| SECONDARY Percentage of Participants Who Died |
14.5; 13.6 | — |
| SECONDARY Overall Survival (OS) |
NA; NA | 0.7767 |
| SECONDARY Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab |
28; 46; 2; 1 | — |
| SECONDARY Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20) |
49; 13 | — |
Eligibility Criteria
Inclusion Criteria
- Adult women greater than or equal to (≥) 18 years of age
- Non-metastatic primary invasive adenocarcinoma of the breast clinical stage I to IIIC, including inflammatory and multicentric/multifocal breast cancer, with tumor size ≥1 centimeter (cm) by ultrasound or ≥2 cm by palpation, centrally confirmed HER2-positive (immunohistochemical score [IHC] 3+ or in situ hybridization [ISH]-positive)
- At least 1 measurable lesion in breast or lymph nodes (≥1 cm by ultrasound or ≥2 cm by palpation), except for inflammatory carcinoma (T4d)
- Baseline left ventricular ejection fraction (LVEF) ≥55%
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- Adequate organ function at Baseline
Exclusion Criteria
- History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma
- Past or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and in situ carcinoma of the cervix
- Metastatic disease
- Any prior therapy with anthracyclines
- Prior anti-HER2 therapy or biologic or immunotherapy
- Serious cardiac illness
- Pregnant or lactating women
Data sourced from ClinicalTrials.gov (NCT00950300) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.